Abstract
BackgroundWe have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose progression over time, independently of known risk factors for diabetes development. However, since MR-ANP levels might be influenced by unknown factors causing diabetes, we cannot rule out that such relationship might be confounded. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the natriuretic peptide precursor A (NPPA) locus gene with higher levels of circulating ANP. Since gene variants are inherited randomly and not subject to confounding, we aimed to investigate whether the variant rs5068 within the NPPA locus is associated with incident type 2 diabetes.MethodsWe genotyped the variant rs5068 within the NPPA locus in 27,307 individuals without known diabetes from the Malmö Diet Cancer Study. Incident diabetes was retrieved through national and regional registers (median follow-up time of 14 years, 2,823 incident diabetes cases).ResultsIn Cox regression analysis adjusted for age, sex and BMI, we found that the carriers of at least one copy of the G allele of rs5068 had lower likelihood of incident diabetes within 14 years (HR = 0.88, 95% CI 0.78–0.99, p = 0.037).ConclusionOur results indicate a role of the ANP system in the etiology of type 2 diabetes and might help provide insight in the metabolic actions of natriuretic peptides and the pathophysiology of type 2 diabetes.
Highlights
The natriuretic peptides (NPs), which are secreted from cardiomyocytes in response to cardiac wall stress, play an important role in the regulation of blood pressure, intravascular volume, and cardiac remodeling
The NPs consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and Ctype natriuretic peptide, where ANP and BNP are secreted by the heart in response to increased volume and pressure load [1]
Large cross-sectional studies have shown lower levels of NP in patients with metabolic syndrome, fasting glucose and insulin resistance [16,17,18] and we recently published data showing that reduced levels of circulating midregional atrial natriuretic peptide (MR-ANP), but not the N-terminal prohormone of brain natriuretic peptide (NT-proBNP), predicted new onset diabetes mellitus (DM) as well as degree of fasting glucose progression over time at the population level, independently of diabetes risk factors and renal function during 16 years of follow-up, suggesting that low ANP might be causally related to diabetes development [5]
Summary
The natriuretic peptides (NPs), which are secreted from cardiomyocytes in response to cardiac wall stress, play an important role in the regulation of blood pressure, intravascular volume, and cardiac remodeling. Large cross-sectional studies have shown lower levels of NP in patients with metabolic syndrome, fasting glucose and insulin resistance [16,17,18] and we recently published data showing that reduced levels of circulating midregional atrial natriuretic peptide (MR-ANP), but not the N-terminal prohormone of brain natriuretic peptide (NT-proBNP), predicted new onset diabetes mellitus (DM) as well as degree of fasting glucose progression over time (defined as the difference between fasting glucose concentration at the reexamination and at the baseline examination divided by the follow up time) at the population level, independently of diabetes risk factors and renal function during 16 years of follow-up, suggesting that low ANP might be causally related to diabetes development [5]. We recently published a study that showed an association of a single nucleotide polymorphism rs5068 on the natriuretic peptide precursor A (NPPA) locus gene with higher levels of circulating ANP as well as lower interindividual blood pressure (BP) [4]. Since gene variants are inherited randomly and not subject to confounding, we aimed to investigate whether the variant rs5068 within the NPPA locus is associated with incident type 2 diabetes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
